The Use of Erythropoietin to Reprogram Oral and Craniofacial Stem Cells

描述(由申请人提供)：使用促红细胞生成素对口腔和颅面干细胞进行重新编程。该项目直接针对挑战领域(14)-干细胞，特别是14-DE-101*口腔和颅面组织细胞的重编程，其中我们开发了一种使用促红细胞生成素(EPO)对口腔和颅面复合体的体细胞进行部分重编程的新方法，用于基于细胞的治疗，以修复和恢复疾病或创伤后的这些组织。我们已经证实EPO在体外和体内都能诱导骨形成。我们还纯化了间充质干细胞(MSC)群体，在体内和体外都保持了其多向分化潜能。最重要的是，我们可以使用细胞表面标记来分离间充质干细胞，这样我们就可以在没有培养的情况下前瞻性地分离细胞。这使我们有别于间充质生物学领域的其他人。在这个项目中，我们将结合我们的两项研究来确定EPO是否可以对成年MSCs进行部分重新编程，用于再生不可愈合的伤口。这项提议将成为我们范式的关键转变，并为应用生物工程控制组织再生提供跳板，我们相信最终将在广泛的人体组织中使用。我们的总体假设是，促红细胞生成素(EPO)可用于重新编程骨骼前体细胞和间充质干细胞，可用于骨骼修复。我们的方法将是确定EPO是否可以用于重新编程骨髓基质细胞，然后是MSCs，以促进不可愈合和辐射的临界大小的骨缺损的骨修复。目的1.确定重组为表达促红细胞生成素的骨髓间充质干细胞在多大程度上能够再生因放射治疗而受损的临界大小的颅面缺损。目的2：确定促红细胞生成素(EPO)能否部分重新编程间充质干细胞(MSCs)进行基于细胞的治疗，以修复和恢复疾病或创伤后的组织。该项目将促进创造就业机会，并加快科学的步伐和成果。该项目在两年的时间内完成是可行的，我们的团队将处于突出的地位，提出并完成更多关于口腔和颅面再生的机械性和翻译性研究。2促红细胞生成素可以用来对骨骼前体和间充质干细胞进行重新编程，这些干细胞可以用于骨骼修复。

DESCRIPTION (provided by applicant): The Use of Erythropoietin to Reprogram Oral and Craniofacial Stem Cells. This project directly addresses Challenge Area (14)-Stem Cells, specifically 14-DE-101* Reprogramming of Cells from Oral and Craniofacial Tissues in which we developed a novel approach for partial reprogramming of somatic stem cells of the oral and craniofacial complex using erythropoietin (Epo) for cell- based therapies to heal and restore these tissues following disease or trauma. We have identified that Epo is able to induce bone formation in vitro as well as in vivo. We have also purified mesenchymal stem cell (MSC) population that maintains its multi-lineage potential both in vivo and in vitro. Most importantly, we can isolate MSCs using cell surface markers that allows us to prospectively isolate the cells without culture. This sets us apart from others in the mesenchymal biology field. In this project we will combined our two studies to determine if Epo can partially reprogram adult MSCs to be used for regeneration of non-healing wounds This proposal will serve as a critical shift in our paradigm and a spring board for application of bioengineering to controlling tissue regeneration that we believe will ultimately be used in a broad range of human tissues. Our overall hypothesis is that erythropoietin (Epo) can be used to reprogram skeletal precursors and mesenchymal stem cells that can be harnessed for skeletal repair. Our approach will be to determine if Epo can be used to reprogram bone marrow stromal cells, and later MSCs, to facilitate osseous repair in nonhealing and irradiated critical sized boney defects. Aim 1. To determine the extent to which BMSCs reprogrammed to express EPO are capable of regenerating critical sized cranio-facial defects compromised by radiation therapy. Aim 2: To determine whether Epo can partially reprogram MSCs for cell-based therapies to heal and restore tissues following disease or trauma. This project will promote job creation, and accelerate the pace and achievement of science. The completion of the project is feasible in a two year timeframe and our group will then be in an outstanding position to propose and complete more mechanistic and translational studies in oral and craniofacial regeneration. 2 Erythropoietin can be used to reprogram skeletal precursors and mesenchymal stem cells that can be harnessed for skeletal repair.